241 - Human carotid atherosclerotic plaque characterization by MALDI mass spectrometry imaging (ID 689)
Abstract
Background and Aims
Atherosclerosis is an arterial disease that is characterized by the gradual build-up of lipids and inflammatory cells in the vascular wall, termed plaque. We hypothesize that specific lipid species can be correlated to plaque phenotype which could have implications for the development of new imaging technologies and new treatment strategies.
Methods
Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) we visualized the spatial distribution of lipids in atherosclerotic plaque tissue sections. Twelve carotid endarterectomy specimens were harvested, cut into 2mm thick cross-sections and cryosectioned, and subsequently imaged using MALDI-MSI (N=106). Data reduction was performed on the data, lipid m/z values present in more than 30% of all tissue sections were retained.
Results
Non-negative matrix factorization (NMF) analysis was performed, representing the lipid variability in 6 components, clustering lipid-classes together in different components. We compared this to adjacent histochemically stained tissue sections, the gold standard of tissue typing in atherosclerotic plaque. We segmented plaque components: necrotic core (NC), fibrin, foam cells, erythrocytes and calcium, registered this to the MALDI tissue section. Multivariate data analysis of NC versus other (not NC) areas generated a classification model (OPLS-DA) for nine patients. Sphingomyelins and oxidized cholesteryl esters were found to be more abundant in NC, consistent with the content and spatial distribution of NMF component 5.
Conclusions
Our findings are consistent with theories on pathogenesis of atherosclerosis, which may make the intensity of these lipids predictive as a marker for vulnerability. Ongoing research is aimed at visualizing lipid composition in vivo for risk stratification and therapy guidance.
